Olanzapine bipolar disorder

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Aripiprazole Blockade of 5HT2A receptors > blockade of D2 receptors Some a blockade (clozapine, risperidone, ziprasidone) and M-receptor blockade (clozapine, olanzapine) variable receptor blockade (all) Schizophrenia—improve both positive and negative symptoms bipolar disorder (olanzapine or risperidone adjunctive with lithium) agitation in Alzheimer s and Parkinson s (low doses) major depression (aripiprazole) Toxicity Agranulocytosis (clozapine), diabetes (clozapine, olanzapine), hypercholesterolemia (clozapine, olanzapine), hyperprolactinemia (risperidone), QT prolongation (ziprasidone), weight gain (clozapine, olanzapine)... 

Olanzapine Alcohol Olanzapine is a second generation antipsychotic used to treat schizophrenia and mania related to bipolar disorder. Olanzapine binds neurotransmitter receptors of several classes including dopaminergic, adrenergic, and serotonergic receptors [249, 250]. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Olanzapine Zyprexa 20, 30 mg Tablets 2.5, 5, 7.5, 10, 5-20 mg/day in 1 or 2 doses combination with lithium or valproate for the acute treatment of mania or mixed states for bipolar I disorder. Olanzapine and aripiprazole are approved for relapse prevention as well as for acute therapy... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

Zyprexa (Olanzapine) Bipolar disorders Gilles de la Tourette s syndrome Psychotic disorders 1.9 0.6 1996 - UK and US Once daily... 

Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. 

Valproate is as effective as lithium and olanzapine for pure mania, and it can be more effective than lithium for rapid cycling, mixed states, and bipolar disorder with substance abuse. It reduces the frequency of recurrent manic, depressive, and mixed episodes. 

Olanzapine (Zyprexa). The olanzapine molecule is structurally very similar to clozapine and therefore exerts very similar effects on brain receptors. The dose range of olanzapine for treating schizophrenia is from 5 to 30mg/day. Like clozapine, olanzapine appears to treat both positive and negative symptoms. It is also approved for the treatment of the manic phase of bipolar disorder. It has also been shown to augment the antidepressant effects of fluoxetine in refractory patients. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Olanzapine Thienobenzodiazepine 5-20 Medium 5 Bipolar disorder PDD Schizophrenia Frazier et ah, 2000 Potenza et ah, 1999 Kumra et ah, 1998... 

Chart reviews and open trials of outpatients with bipolar disorder and bipolar spectrum disorder have been published for 28 risperidone- and 23 olanzapine-treated treated children and adolescents (Frazier et ah, 1999 2001). Significant decreases in mania, depression, and aggression ratings occurred over the course of treatment however, other medications were also used simultaneously. Additional anecdotal information exists for olanzapine (Soutullo et ah, 1999 Chang and Ketter, 2000), quetiapine (Schaller and Behar, 1999), and clozapine (Fuchs, 1994). 

Frazier, J.A., Biederman, J., Tohen, M., Feldman, P.D., Jacobs, T.G., Toma, V., Rater, M.A., Tarazl, R.A., Kim, G.S., Garfield, S.B., Sohma, M., Gonzalez-Heydrlch, J., Rlsser, R.C., and Nowlin, ZM (2001) A prospective open-label trial of olanzapine monotherapy in children and adolescents with bipolar disorder. / Child Adolesc Psychoparmacol 11 239-250. 

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

In four instances, the agency has invoked this rule at the time of approval of supplements for new indications for psychotropic drugs already approved for other psychiatric indications. It was noted in the approval letters for these supplements that, since the drugs in question would likely be used in children and/ or adolescents with the newly approved indications, the FDA required the sponsors of these products to conduct studies that would be pertinent to such use in the pediatric population. Since the products were ready for approval in adults, the FDA deferred the required pediatric studies to a future date. Alternatively, sponsors could make an argument for waiver of the requirement. The drug products and indications for which the FDA has required studies under the Pediatric Rule are as follows paroxetine for social anxiety disorder sertraline for post-traumatic stress disorder (PTSD) olanzapine for acute mania in bipolar disorder and fluoxetine in premenstrual dysphoric disorder (PMDD). 

The olanzapine-fluoxetine combination is currently the only medication approved by the FDA specifically for the treatment of depression in patients with bipolar disorder. This indication was based on data from a double-bhnd, randomized study in which the combination was superior to both olanzapine monotherapy and placebo (Tohen et al. 2003). Treatment-emergent mania or hypomania did not occur more frequently in the olanzapine-fluoxetine combination group than in the placebo group during the acute trial. 

Several controlled trials have shown that lithium is efficacious in the maintenance treatment of bipolar disorder, with higher serum levels (0.8 1 mol/1) being more indicative of successful prophylaxis (Keck and McElroy. 2002). Valproic acid also appears to have efficacy in maintenance therapy, specifically in bipolar patients with mixed mania and rapid cycling (Bowden et al., 1995). The results concerning carbamazepine s efficacy as a maintenance medication are controversial (Stuppaeck et al., 1994). Other potential agents with some evidence of good maintenance value include clozapine and olanzapine. A combination of lithium and carbamazepine or other anticonvulsants is recommended under certain conditions if an adequate preventive effect cannot be obtained with the substances individually (Bauer et al., 2002). 

Tohen. M.. Baker. R.W., Milton. D.R., et al. Olanzapine versus divalproex sodium for the treatment of acute mama. Bipolar Disorders 3, 60-61, 2001. 

We would emphasize that, while all of these approaches are theoretically important and may possess clinical applicability, with the exception of the atypical antipsychotic olanzapine, none is presently approved by the FDA for treatment of bipolar disorder. 

Frazier JA, Biederman J, Jacobs TG, et al. Olanzapine in the treatment of bipolar disorder in Juveniles. Presented at the American Psychiatric Association Annual Meeting, Chicago, May 13-18, 2000. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Fig. 11—40) and clinical features, not only as compared with clozapine (Fig. 11 — 37) but also as compared with risperidone (Fig. 11—39)- Olanzapine is atypical in that it generally lacks EPS, not only at moderate doses but usually even at high doses. Thus, olanzapine tends to be used for some of the most difficult cases of schizophrenia, bipolar disorder, and other types of psychosis in which good control of psychosis without EPS is still desired, yet aggressive treatment is required. On the other hand, this approach can be very expensive. 

Vieta E, Sanchez-Moreno J, Goikolea JM, Colom F, Martinez-Aran A, Benabarre A, Corbella B, Torrent C, Comes M, Reinares M, Brugue E. Effects of weight and outcome of long-term olanzapine-topiramate combination treatment in bipolar disorder. J Clin Psychopharmacol 2004 24 374-8. 

Seager, M. A., Barth, V. N., Phebus, L. A. Rasmussen, K. (2005). Chronic coadministration of olanzapine and fluoxetine activates locus coeruleus neurons in rats Implications for bipolar disorder. Psychopharmacology (Berl), 181, 126-133. 

Valproate + olanzapine IV Bipolar disorder Abbott Laboratories... 

---